All posts by administrador

2018, Publicación, TosMIC

Gutierrez et al. J Org Chem. 2018;83(12):6623-6632. gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Publications > Gutierrez et al

J Org Chem. 2018, 83, 6623 PubMed 29756452

gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Sara Gutierrez, David Sucunza, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica and Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 - Alcala de Henares , Madrid , Spain.

Abstract

A new method for the synthesis of gamma-carbolines by a heterocyclization that involves alpha-indol-2-ylmethyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to the synthesis of several highly substituted gamma-carbolines.

2018, Publicación

Malvicini et al. Mol Cancer Ther. 2018;17(5):966-976. A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response.

Publications > Malvicini et al

Mol Cancer Ther. 2018 May;17(5):966-976. doi: 10.1158/1535-7163.MCT-17-0193. Epub 2018 Feb 26. PubMed 29483221

A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response.

Mariana Malvicini1, Ana Gutierrez-Moraga2, Marcelo M Rodriguez3, Sofia Gomez-Bustillo1, Lorena Salazar1, Carlos Sunkel2, Leonor Nozal2, Antonio Salgado4, Manuel Hidalgo4, Pedro P Lopez-Casas5, Jose Luis Novella6, Juan Jose Vaquero4, Julio Alvarez-Builla4, Adda Mora4, Manuel Gidekel7, Guillermo Mazzolini2, a

1. Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomedicas, CONICET- Universidad Austral, Buenos Aires, Argentina.  2. Universidad Autonoma de Chile, Providencia, Chile.  3. Universidad de La Frontera, Temuco, Chile.  4. Departamento de Quimica Organica, Universidad de Alcala, Madrid, Spain.  5. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.  6. Gastrointestinal Cancer Clinical Research Unit, CNIO - Spanish National Cancer Research Center, Madrid, Spain.  7. Creative BioScience, Huechuraba, Santiago, Chile.

a. gmazzoli@cas.austral.edu.ar, mgidekel@creativebio-science.com

Abstract

In colorectal carcinoma patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic colorectal carcinoma have incurable disease; therefore, new therapies are needed. Agents derived from medicinal plants have already demonstrated therapeutic activities in human cancer cells. Antartina is an antitumor agent isolated from Deschampsia antarctica Desv. This study aimed to evaluate the antitumor properties of Antartina in colorectal carcinoma models. We used human and murine colorectal carcinoma cell lines for investigating proliferation, apoptosis, and cell-cycle effects of Antartina therapy in vitro Avatar and immunocompetent colorectal carcinoma animal models were applied for evaluating the effects of Antartina in vivo Immune response against colorectal carcinoma model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T-cell subpopulation, and by tumor rechallenge experiments. Antartina inhibits in vitro human colorectal carcinoma cell proliferation; however, in vivo experiments in Avatar colorectal carcinoma model Antartina display a limited antitumor effect. In an immunocompetent colorectal carcinoma mice model, Antartina potently inhibited tumor growth and liver metastases, leading to complete tumor regressions in >30% of mice and increased animal survival. In addition, Antartina induced a potent specific cytotoxic T-cell response against colorectal carcinoma and a long-lasting antitumor immunity. Interestingly, Antartina increased tumor immunogenicity and stimulated dendritic cell activation. No toxic effects were observed at the doses employed. Our findings showed that Antartina has the ability to induce antitumor immunity against colorectal carcinoma and can be used to develop new tools for the treatment of colorectal carcinoma. Mol Cancer Ther; 17(5); 966-76. (c)2018 AACR.

2018, BioImag, Publicación

Bosch et al. Org. Chem. Front.. 2018;5(12):1916-1927. Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes.

Publications > Bosch et al

Org. Chem. Front. 2018, 5, 1916

Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes.

Pedro Bosch1, David Sucunza1, Francisco Mendicuti2, Alberto Domingo3, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Spain.  2. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Spain.  3. Departamento de Biología de Sistemas, Universidad de Alcalá, Spain.

Abstract

Steady-state and time-resolved fluorescence, circular dichroism and molecular modelling techniques have been applied to a new family of weakly fluorescent dibenzopyridoimidazocinnolinium derivatives whose fluorescence intensity increases significantly (larger than × 3.5) upon DNA addition. The synthesis of these azonia cations, which bind to DNA by intercalation, was carried out using a Westphal condensation and a Suzuki cross coupling reaction as key steps. A live-cell staining analysis by confocal microscopy imaging was also performed and showed the capacity of these new compounds for active uptake and accumulation by living cells, with complex patterns of intracellular distribution observed.

2018, AzaBN, Publicación

Abengozar et al. Chem Commun (Camb). 2018;54(20):2467-2470. Synthesis of functionalized helical BN-benzo[c]phenanthrenes.

Publications > Abengozar et al

Chem Commun 2018, 54, 2467 PubMed 29319090

Synthesis of functionalized helical BN-benzo[c]phenanthrenes.

Alberto Abengozara, Patricia Garcia-Garcia, David Sucunza, Adrian Perez-Redondo, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR), Universidad de Alcala, 28805-Alcala de Henares, Madrid, Spain.

a. patricia.garciagarci@uah.es, juanjose.vaquero@uah.es

Abstract

A novel parent BN-benzo[c]phenanthrene, with helical chirality and remarkable structural features, has been easily obtained in three steps with a global yield of 55%. Moreover, Cl-substituted derivatives have been prepared and these have served as useful starting materials for the development of palladium-catalyzed cross-coupling reactions.

2017, BioImag, Publicación

Cañeque et al. Dyes and Pigments. 2017;:17-31. Azonia aromatic heterocycles as a new acceptor unit in D-π-A%@2B vs D-A%@2B nonlinear optical chromophores.

Publications > Cañeque et al

Dyes Pigm. 2017, 144, 17

Azonia aromatic heterocycles as a new acceptor unit in D-π-A%@2B vs D-A%@2B nonlinear optical chromophores.

Tatiana Cañeque1, Ana M. Cuadro1, Raúl Custodio1, Julio Alvarez-Builla1, Belén Batanero1, Pilar Gómez-Sal1, Javier Pérez-Moreno2, Koen Clays3, Obis Castaño4, José L. Andrés4, Thais Carmona4, Francisco Mendicuti4, Juan J Vaquero1

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  2. Department of Physics, Skidmore College, Saratoga Springs, NY, United States.  3. Department of Chemistry, University of Leuven, Celestijnenlaan 200 D, 3001, Leuven, Belgium.  4. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.

Abstract

A comparison of D-π-A%@2B and D-A%@2B cationic chromophores based on the quinolizinium system as new acceptor units is reported along with the results of studies into their linear and non-linear optical properties and electrochemical data. Experimental and theoretical data show that quinolizinium-based chromophores may provide a new generation of second-order non-linear materials with enhanced performance. The first hyperpolarizabilities were measured by Hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis. In some chromophores the absence of a bridge (D-A%@2B) between the donor and acceptor fragments enhances the NLO properties and the single crystal structure of such a material has been determined by X-ray diffraction.

2017, Publicación

Martín et al. Journal of Analytical and Applied Pyrolysis. 2017;:278-285. Microwave-assisted pyrolysis of Mediterranean forest biomass waste: Bioproduct characterization.

Publications > Martín et al

J Anal Appl Pyrolysis 2017, 127, 278

Microwave-assisted pyrolysis of Mediterranean forest biomass waste: Bioproduct characterization.

María T. Martín1, Ana B. Sanz2, Leonor Nozal2, Flor Castro2, Raúl Alonso2, Juan L. Aguirre1, Sergio D. González1, M. Paz Matía2, José L. Novella2, Manuel Peinado1, Juan J Vaquero3

1. Cátedra de Medio Ambiente, Facultad de Biología, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.  2. Centro de Química Aplicada y Biotecnología, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.  3. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.

Abstract

Different types of forest and scrub biomass waste that are representative of the Mediterranean biogeographical region (Pinus pinaster, Quercus ilex, waste from forestry activities in pinewoods and Cistus ladanifer) were pyrolyzed in a batch microwave reactor. The pyrolysis conditions were optimized using Pinus pinaster as the raw material. All experiments were performed at 400W with 7.5% biochar as a microwave absorber. Under these conditions four fractions were characterized: a non-condensable gas fraction, a bio-liquid composed of separable organic and aqueous soluble components and biochar. All liquid and gas fractions were characterized by gas chromatography/mass spectrometery (GC/qMS) to identify the main components. The bioliquid organic fraction was distilled and a bio-bitumen residue was collected. The rheological properties of this residue were studied. Biochar was characterized by measuring the specific surface area in order to assess its adsorptive properties. Mass distribution was calculated according to the feedstock.

2017, AzaBN, Publicación

Abengozar et al. Org Lett. 2017;19(13):3458-3461. Synthesis, Optical Properties, and Regioselective Functionalization of 4a-Aza-10a-boraphenanthrene.

Publications > Abengozar et al

Org Lett. 2017, 19, 3458 PubMed 28605913

Synthesis, Optical Properties, and Regioselective Functionalization of 4a-Aza-10a-boraphenanthrene.

Alberto Abengozar1, Patricia Garcia-Garcia1, David Sucunza1, Luis Manuel Frutos2, Obis Castano2, Diego Sampedro3, Adrian Perez-Redondo1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala , 28871 Alcala de Henares, Madrid, Spain.  2. Departamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Universidad de Alcala , 28871 Alcala de Henares, Madrid, Spain.  3. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ), Universidad de La Rioja , Madre de Dios 53, 26006 Logrono, Spain.

Abstract

4a-Aza-10a-boraphenanthrene has been synthesized in only four steps from commercially available materials with a remarkable overall yield of 62%. In contrast to other BN-isosteres of phenathrene, this isomer is weakly fluorescent, which has been explained by means of computational studies that found a low energy conical intersection for the nonradiative deactivation of the excited state. Moreover, a completely regioselective functionalization of 4a-aza-10a-boraphenanthrene at C-1 by reaction with activated electrophiles has been achieved.

2017, BioImag, Publicación

Bosch et al. Dyes and Pigments. 2017;:135-146. Imidazopyridinium cations: A new family of azonia aromatic heterocycles with applications as DNA intercalators.

Publications > Bosch et al

Dyes Pigm. 2017, 138, 135

Imidazopyridinium cations: A new family of azonia aromatic heterocycles with applications as DNA intercalators.

Pedro Bosch1, Verónica García2, Başak S. Bilen3, David Sucunza1, Alberto Domingo2, Francisco Mendicuti3, Juan J Vaquero1

1. Departamento de Química Inorgánica y Química Orgánica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  2. Departamento de Biología de Sistemas, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  3. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.

Abstract

Two novel imidazopyridinium cations formed by a hexacyclic azonia aromatic system have been synthesized. Spectrofluorimetric titrations, circular dichroism measurements, theoretical simulations and fluorescence-based thermal denaturation experiments on these materials have shown the interesting fluorescence properties and DNA-binding ability by intercalation, with a marked preference for AT-rich sequences. Compound 2 presents the highest fluorescence quantum yield (0.32 in 5% DMSO/water and 0.46 in MeOH) and affinity for DNA (binding constant of ∼4.5 × 105 M−1). Moreover, the potential of these compounds for cell staining has been investigated in living HeLa cells by confocal microscopy imaging. This analysis showed the remarkable capacity of both compounds for uptake and accumulation by living cells.

2017, BioImag, Publicación

Zacharioudakis et al. Biorg. Med. Chem. Lett.. 2017;:203-207. Quinolizinium as a new fluorescent lysosomotropic probe.

Publications > Zacharioudakis et al

Biorg. Med. Chem. Lett. 2017, 27, 203

Quinolizinium as a new fluorescent lysosomotropic probe.

Emmanouil Zacharioudakis1, Tatiana Cañeque2, Raúl Custodio3, Sebastian Müller1, Ana M. Cuadro2, Juan J Vaquero2, Raphaël Rodriguez1

1. Institut Curie, PSL Research University, Organic Synthesis and Cell Biology Group, 26 rue d’Ulm, 75248 Paris Cedex 05, France, CNRS UMR3666, 75005 Paris, France, INSERM U1143, 75005 Paris, France.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  3. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Abstract

We have synthesized a collection of quinolizinium fluorescent dyes for the purpose of cell imaging. Preliminary biological studies in human U2OS osteosarcoma cancer cells have shown that different functional groups appended to the cationic quinolizinium scaffold efficiently modulate photophysical properties but also cellular distribution. While quinolizinium probes are known nuclear staining reagents, we have identified a particular quinolizinium derivative salt that targets the lysosomal compartment. This finding raises the question of predictability of specific organelle targeting from structural features of small molecules.

2017, Publicación

Vasilev et al. Beilstein J Org Chem. 2017;13:2902-2914. Halogen-containing thiazole orange analogues – new fluorogenic DNA stains.

Publications > Vasilev et al

Beilstein J. Org. Chem. 2017, 13, 2902 PubMed 29564018

Halogen-containing thiazole orange analogues - new fluorogenic DNA stains.

Aleksey A Vasilev1, Meglena I Kandinska2, Stanimir S Stoyanov2, Stanislava B Yordanova2, David Sucunza3, Juan J Vaquero3, Obis D Castano3, Stanislav Baluschev4, Silvia E Angelova3

1. Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1 James Bourchier Blvd., 1164 Sofia, Bulgaria.  2. Department of Organic Chemistry and Pharmacognosy, Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1 James Bourchier Blvd., 1164 Sofia, Bulgaria.  3. Departments of Organic and Physical Chemistry, University of Alcala, 28871-Alcala de Henares, Madrid, Spain.  4. Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.

Keywords: DFT calculations; cyanine dyes; green synthesis; nucleic acids; thiazole orange

Abstract

Novel asymmetric monomeric monomethine cyanine dyes 5a-d, which are analogues of the commercial dsDNA fluorescence binder thiazole orange (TO), have been synthesized. The synthesis was achieved by using a simple, efficient and environmetally benign synthetic procedure to obtain these cationic dyes in good to excellent yields. Interactions of the new derivatives of TO with dsDNA have been investigated by absorption and fluorescence spectroscopy. The longest wavelength absorption bands in the UV-vis spectra of the target compounds are in the range of 509-519 nm and these are characterized by high molar absorptivities (63000-91480 L.mol(-1).cm(-1)). All investigated dyes from the series are either not fluorescent or their fluorescence is quite low, but they become strongly fluorescent after binding to dsDNA. The influence of the substituents attached to the chromophores was investigated by combination of spectroscopic (UV-vis and fluorescence spectroscopy) and theoretical (DFT and TDDFT calculations) methods.